Formal synthesis of the ACE inhibitor benazepril x HCl via an asymmetric aza-Michael reaction

Luo-Ting Yu; Ji-Ling Huang; Ching-Yao Chang; Teng-Kuei Yang

doi:10.3390/11080641

Formal synthesis of the ACE inhibitor benazepril x HCl via an asymmetric aza-Michael reaction

Molecules. 2006 Aug 23;11(8):641-8. doi: 10.3390/11080641.

Authors

Luo-Ting Yu¹, Ji-Ling Huang, Ching-Yao Chang, Teng-Kuei Yang

Affiliation

¹ Laboratory of Organometallic Chemistry, East China University of Science & Technology, Shanghai, 200237, P.R. China.

Abstract

A formal enantioselective synthesis of benazepril.HCl (4), an anti- hypertensive drug, is reported. Our synthesis employed an asymmetric aza-Michael addition of L-homophenylalanine ethyl ester (LHPE, 1) to 4-(2-nitrophenyl)-4-oxo- but-2-enoic acid methyl ester (6) as the key step to prepare (2S,3'S)-2-(2-oxo-2,3,4,5- tetrahydro-1H-benzo[b]azepin-3-ylamino)-4-phenylbutyric acid ethyl ester (8), which is the key intermediate leading to benazepril x HCl (4).

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / chemical synthesis*
Angiotensin-Converting Enzyme Inhibitors / chemistry
Benzazepines / chemical synthesis*
Benzazepines / chemistry
Models, Chemical*
Solvents / chemistry

Substances

Angiotensin-Converting Enzyme Inhibitors
Benzazepines
Solvents
benazepril